In this project, we will identify new urinary biomarkers for use in epidemiological studies of women's reproductive health. More sensitive laboratory assays will be developed for biomarkers of ovarian function and early fetal loss (EFL). Immunoassays for urinary human chorionic gonadotropin (hCG), follicle stimulating hormone (FSH), and subunits, as well as assays for luteinizing hormone (LH) and FSH bioactivity in urine will be developed. Prediction rules based on multiple biomarkers of trophoblastic and ovarian function will be used to identify previously unrecognized EFL in population-based studies. A similar approach will be used to identify anovulatory cycles in studies of menstrual function and infertility. Clinical research studies will provide basic information to be used in developing methodology for identifying the target organ of toxicity in cases of ovulation failure and EFL. The environmental and lifestyle variables which may affect these outcomes will be studied in a population of free-living women. The goal of this project is to enable epidemiologists to extend their observations beyond the identification of adverse effects and allow them to focus on the target of reproductive toxicity at the organ system level.